Synthesis of polyamines, which are essential to tissue growth and proliferation, is sensitively controlled by the activity of the enzyme, ornithine decarboxylase. The mechanism of regulation of this enzyme is being investigated in the simple eukaryote, Physarum polycephalum, which has a polyamine synthetic pathway similar to mammalian systems, yet is much more amenable to biochemical manipulation. Preliminary work demonstrated that variations in ornithine decarboxylase activity are associated with the reversible modification of the enzyme between an active and a less active form. These two ornithine decarboxylase forms are distinguished by their large difference in affinity for coenzyme, and the tendency of the less active form to run with the blue dextran dye on Sephadex column chromatography. The biochemical differences between these forms, as well as the exact mechanism of this interconversion, are currently being investigated. Clarification is being sought for the function of regulatory protein subunits, cyclic nucleotides and divalent cation interactions in this modification. Also, demonstrated polyamine synthesis inhibitors, polyamines and promising polyamine analogs are being tested for their precise effect on this relatively complex regulatory mechanism.